Opiate peptides, interacting with m opiate receptors (MORs), affect food intake. One explanation for the basis of these effects is that they influence food palatability. Forebrain structures, especially nucleus accumbens and the ventral pallidum, comprise a critical substrate for the effect of MORs on feeding. Nevertheless, endorphins also impact eating through brainstem circuits, although the loci, effects, and mechanisms of these influences are less clear. One candidate brainstem region includes taste neurons in the rostral nucleus of the solitary tract (rNST) and oromotor circuitry in subjacent reticular formation (RF), a functionally-integrated region that we call the "rostral solitary complex" (RSC). Previous studies suggest that injecting MOR agonists into this vicinity increases food intake whereas antagonists have the opposite effect. Preliminary data with more precise injections and behavioral measures, however, instead suggest that MOR agonist infusions into the RSC exert multiple influences, including immediate effects more indicative of a suppression of feeding. We hypothesize that these complex effects reflect the interaction of these ligands at multiple points in this heterogeneous circuitry. The goal of the present proposal is to precisely define the behavioral consequences of manipulating MORs in the rNST and subjacent RF and to specify the sites and cellular basis of these effects. The Specific Aims are to: (1) Analyze the sensory and motor consequences of manipulating MORs in the rNST and subjacent RF by making small (60nl) infusions of MOR agonists (DAMGO) and antagonists (CTOP), and using multiple behavioral measures, including taste reactivity and short-term taste preference tests. (2) Establish the impact of local injections of DAMGO and CTOP on single-unit gustatory and oral somatosensory responses in the rNST and RF in an in vivo preparation, and (3) Perform in vitro, patch-clamp recordings from the rNST and subjacent RF to characterize the cellular basis of MOR modulation of neurons identified by their afferent and efferent connectivity. Previous work, including studies completed during the last project period, has clarified neurophysiological response properties and connectivity of brainstem taste neurons but knowledge about neurotransmitter function in central taste circuits is scarce. The proposed experiments will begin to fill this void. Moreover, these studies will contribute to understanding of the neural control of feeding, a behavior profoundly impacting human health. The neural substrate regulating eating is complex, involving interactions between multiple regions and levels of the central nervous system. Taste has a major influence on this behavior and the rNST is the 1st central site where these sensory signals are processed. The underlying RF contains motor circuitry comprising a final common pathway that integrates forebrain and hindbrain signals determining whether food intake continues or is aborted. The goal of this proposal is to understand how one class of neuromodulators important in feeding, m opiate ligands, interact at these critical nodes. PUBLIC HEALTH RELEVANCE: The rostral portion of the nucleus of the solitary tract is the initial termination site of all primary afferent fibers conveying gustatory information. Good nutrition is critical to health, and the sense of taste profoundly impacts the type and amount of food eaten. This project will focus on how one class of opiate peptides known to promote eating, influences this region of the brain.